Journal article

miR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation

  • Rusca, Nicole Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Dehò, Lorenzo Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Montagner, Sara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Zielinski, Christina E. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Sica, Antonio Istituto Clinico Humanitas, Rozzano, Italy - Dipartimento di Scienze del Farmaco, Universita' del Piemonte Orientale A. Avogadro, Novara, Italy
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Monticelli, Silvia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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    12.10.2012
Published in:
  • Molecular and cellular biology. - 2012, vol. 32, no. 21, p. 4432-4444
English The transcription factor NF-κB regulates the expression of a broad number of genes central to immune and inflammatory responses. We identified a new molecular network that comprises specifically the NF-κB family member NF-κB1 (p50) and miR-146a, and we show that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell memory formation. Increased mast cell survival was due to unbalanced expression of pro- and antiapoptotic factors and particularly to the complete inability of p50- deleted mast cells to induce expression of miR-146a, which in the context of mast cell survival acted as a proapoptotic factor. Interestingly, in a different cellular context, namely, human and mouse primary T lymphocytes, miR-146a and NF-κB p50 did not influence cell survival or cytokine production but rather T cell expansion and activation in response to T cell receptor (TCR) engagement. Our data identify a new molecular network important in modulating adaptive and innate immune responses and show how the same activation-induced microRNA (miRNA) can be similarly regulated in different cell types even in response to different stimuli but can still determine very different outcomes, likely depending on the specific transcriptome.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318847
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